This invention relates generally to the field of chemical screening, and in particular to the screening of various chemicals for biological or other activity. More specifically, the invention relates to assays where nuclear magnetic resonance is employed as a screening tool.
Modern chemistry has proven to be effective in creating a wide assortment of chemicals that may be useful for a variety of applications including drug therapy, industrial manufacturing, painting, and the like. A recent development in the field of modern chemistry is that of combinatory chemistry where vast libraries of chemical compounds may rapidly be created. For example, combinatorial chemistry techniques are described in U.S. Pat. No. 5,503,805, the complete disclosure of which is herein incorporated by reference.
One significant challenge for the modern chemist is the ability to find useful applications for the vast libraries of chemicals now being created. For example, the drug discovery industry is currently expending significant resources to identify chemicals that may be used as drugs to treat a wide variety of ailments. In order to determine whether a chemical will be useful for a particular application, the chemical needs to be tested in a particular environment to determine if the chemical is active under certain conditions, often referred to as screening. This can be particularly challenging if the number of chemicals to be screened is large. For example, Wilhelm Stahl, "What is the Future of High Throughput Screening?" Journal of Biomolecular Screening, Volume 4, Number 3, pp. 117-118, 1999; Anthony M. Maffia III et. al, "Miniaturization of a Mammalian Cell-Based Assay: Luciferase Reporter Gene Readout in a 3 Microliter 1536-Well Plate", Journal of Biomolecular Screening, Volume 4, Number 3, pp. 137-142, 1999; and Laura Abriola et al., "Digital Imaging as a Detection Method for a Fluorescent Protease Assay in 96-Well and Miniaturized Assay Plate Formats", Journal of Biomolecular Screening, Volume 4, Number 3, pp. 121-127, 1999, the complete disclosures of which are herein incorporated by reference, describe the challenges associated with the demand to increase high throughput screening.
Various types of assays have been developed to screen chemicals for activity at the cellular level. For example, some assays that have been utilized include cell reporter assays, such as lawn assays, direct binding assays, and the like. Further, various types of chemical handling devices and automated equipment have been developed to increase the throughput or efficiency of the screening process. For example, many assays utilize multiwell plates, such as standard 96 well plates where 96 chemicals may be screened in parallel. Other equipment used to facilitate such assays includes robots for plate and chemical handling, plate readers employing CCD cameras, and the like. Merely by way of example, useful apparatus and equipment are described in U.S. Pat. No. 5,722,470 and in copending U.S. patent application Ser. No. 08/834,803, filed Apr. 3, 1997, the complete disclosures of which are herein incorporated by reference.
Even so, there is still a need for other techniques to screen for biological or other activity in a high throughput manner, particularly in view of the large chemical libraries now being created. Further, a need also exists for new assays and associated screening techniques that may be used to screen chemicals for certain types of activity. Hence, the invention is related to alternative assays and screening techniques that are particularly adapted for high throughput screening and/or for providing alternative avenues to screen for certain types of activity.